The ventral anterior (VA) and ventral medial (VM) thalamic nuclei are the site of overlap of projections from the basal ganglia (substantia nigra and globus pallidus), cerebellum and motor and premotor areas of the neocortex. The goal of this proposal is to determine how the synaptic organization of these inputs changes when the VA and VM are deafferented from the nigra and/or pallidum. It is suggested that some kind of plasticity type changes (i.e. reactive synaptogenesis) may take place as a result of such deafferentation which will lead to formation of abnormal circuitry in the thalamus. This experimental situation may be to some extent very similar to what occurs during the pathogenesis of some dyskinetic disorders, particularly Parkinsonism. The study will be carried out in cats using EM neuroanatomical techniques (degeneration, autoradiography of orthogradely transported leucine, and retrograde HRP transport). The qualitative and quantitative ultrastructural analysis of the VA and VM will be performed at different survival times (from 2 days to 2 months) after electrolytic lesions in the pars reticularis of substantia nigra and/or kainic acid injections in the entopeduncular nucleus. If after deafferentation changes are observed in some type(s) of intact axon terminals (increase in density of boutons per mm.2, increase in size of boutons or in number of synaptic active zones; shift in location of synaptic sites along the soma-dendritic membrane of thalamic neurons, etc.) the afferent origin of these axon terminals will be determined or confirmed by EM autoradiography (after 3H-leucine injections in the afferent structure under question) and HRP experiments (injections in the deafferented thalamic nuclei). The results will reveal whether a potential for synaptic remodeling exists in the thalamus after deafferentation from inhibitory basal ganglia inputs, what the concrete mechanism of this remodeling is and which intact afferent systems occupy the denervated sites. It is expected that these results will provide essential anatomical background for understanding the role of basal ganglia inputs to the thalamus in the pathogenesis of dyskinetic disorders. The realization of the project is facilitated by the fact that substantial amount of background data on the normal synaptic organization of the VA and VM have already been obtained in our laboratory.